Migraine headache remains a treatment dilemma in headache clinics, pain clinics, and emergency departments throughout the country. In the late nineties, investigators reported that a standard hypnotic anesthetic, propofol (2,6 di-isopropylphenol), dramatically improved pain scores of patients suffering from refractory migraine headaches [1–3]. Case reports over the last few years have appeared in the medical literature describing the use of propofol for migraine treatment. Dosing regimens are not clear, and mechanisms of action to terminate or markedly curtail ongoing intractable headaches are not described. This case report, of two hospitalized patients with refractory migraine, increases the existing literature on the use of propofol therapy in migraine headache. In the first case, three different scenarios and dosages are described in the same patient. In the second case, the use of different dosages of propofol is described. A self-reported scale was employed by the patients to determine the efficacy of propofol therapy. In the first case, the patient's self-reported migraine score was an average of 100/100 and decreased to 10/100. In the second case, the patient's self-reported migraine score improved from 92/100 to 40/100. We propose that the improvements in the self-reported migraine score in both patients after propofol therapy may be due to GABAA agonist effects and cerebral vasoconstriction.